November 10-15

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ACR Convergence 2023

San Diego, CA

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Lupus needs more treatment options, better trial designs


3 minutes

Although lupus survival has improved throughout the years, presenters in the Monday session Lupus Treatment: B Cells, Interferon & More emphasized that a serious need remains for new treatments and better trial designs.

David Isenberg, MD, FRCP, Professor of Rheumatology, University College London, specifically addressed targeting B cells with rituximab, noting B cell depletion was first used to treat patients with lupus 20 years ago. Rituximab is approved in the United Kingdom for lupus treatment, but not in the United States, and generally works for many lupus patients, despite the failure of two large double-blind controlled clinical trials, he said.

“The use of this is recommended by both the ACR and the EULAR guidelines for the treatment of lupus nephritis,” Dr. Isenberg said. “I think it’s reasonable to assume the communities that made these suggestions would not have done so unless they were convinced by the evidence. … rituximab is clearly widely used for many aspects of lupus, but I have to emphasize (again) that it does not work in about 10% of our patients, and you have to be aware of hypogammaglobulinemia and allergic responses.”

The notion of combination therapy for lupus treatment is starting to be evaluated and something to keep an eye on, he added. This is being tested in the BEAT-LUPUS trial, where all 50 patients were given rituximab, and half each were given subsequent belimumab or placebo. The results are expected in 2020.

Richard Furie, MD, Chief of the Division of Rheumatology at Northwell Health and Professor of Medicine, Zucker School of Medicine at Hofstra/Northwell, addressed the innate immune system, particularly interferons, and how they are potentially targets for lupus drug treatment. Dr. Furie reminded attendees there are three different types of interferons and noted that type 1 has five subtypes. 

“A very key point to remember is that all subtypes bind to the same receptor,” Dr. Furie said.

Dr. Furie reviewed the various strategies for inhibiting interferons, including extracellular targets, intracellular targets, and post-translational targets. 

“Despite the ups and downs in lupus — clinical trials have been so challenging and we’ve been doing this since the early 1990s — but we’re making progress, bit by bit,” he said. “I do think the future is bright for our patients.”

Daniel Wallace, MD, FACP, MACR, Professor of Medicine and Associate Director Rheumatology Fellowship Program at Cedars-Sinai Medical Center at the David Geffen School of Medicine at UCLA, iterated just how complicated trial design can be for lupus because of its heterogeneity, and echoed the other presenters about how more new drugs are needed for lupus because of its unacceptably high morbidity and mortality rate. Twenty phase II/III trials have failed to meet their endpoints for various reasons, including bad implementation, failed design, or the drug lacked safety or efficacy. Dr. Wallace addressed ways to help clinical trials by designing them not related to mechanism of action but by what the intent is. 

“It’s been suggested that we abandon the FDA guidelines, and they’re going along with it, too, and that we need approaches where we have smaller studies that either prevent the development of the disease, such as the SMILE study … or induction therapy for early/active disease, maintaining improvement, preventing flare, or just organ systems-specific treatment,” he said.

Dr. Wallace, who estimated that roughly $10 billion has been spent on failed efforts of lupus treatment, also briefly discussed a group working on a new lupus outcome measure to help accurately measure and accelerate the approval process.